The tumors that derive from normal liver, cartilage, or muscle cells each have very different properties. Malignant cells, including the most "undifferentiated" or "anaplastic", retain to varying degrees genetic properties characterizing their cell of origin. Tumor cells do not return to a more "primitive" or "embryonic" state; rather they represent a further stage in the evolution of a particular cell lineage. This proposal describes experiments stressing the obligatory requirement for DNA synthesis and ensuing "quantal" cell cycles in moving normal differentiating cells from one compartment in a cell lineage to the next. It is proposed that one quantal cell cycle is required to transform a normal mother cell into a malignant daughter cell, and that subsequent increase in numbers of that malignant cell involves a series of proliferative cell cycles. Experiments are outlined using BuDr, PMA, and a variety of labelled precursors to proteins and nucleic acids to follow aspects of normal differentiation of myogenic, chondrogenic, and melanogenic cells, particularly as related to (1) DNA synthesis, and (2) experiments using the same methodologies and theoretical concepts to follow the transformation of these same cell types into malignant cells. These experiments involve using a temperature-sensitive mutant of the Rous Sarcoma virus, as well as following the changes induced by phorbal esters and frank carcinogens.